The invention relates to processes for the preparation of 4,5-bisimino-[1,3]dithiolanes and 2,3-bisimino-[1,4]dithianes. Certain of these processes have two-step sequences involving (i) conversion of an oxalamide to a dithiooxalamide, followed by (ii) conversion of the dithiooxalamide to either a 4,5-bisimino-[1,3]dithiolane or a 2,3-bisimino-[1,4]dithiane. 4,5-bisimino-[1,3]dithiolanes and 2,3-bisimino-[1,4]dithianes are useful as ligands for olefin polymerization catalysts (U.S. Pat. No. 6,103,658; PCT Intl. Appl. WO 0050470A2).
Nickel and palladium complexes of bidentate N,N-donor ligands have recently been shown to be useful as olefin polymerization catalysts (Ittel et al., Chem. Reviews 2000, 100, 1169). There is a need therefore for efficient methods of synthesizing such ligands. In addition to the methods described in the literature reviewed by Ittel et al. (Chem. Reviews 2000, 100, 1169), Gonioukh et al. (WO 01/21586 A1) have recently described methods for this purpose. Notwithstanding these developments, there remains a need for further improvements in efficiency and scope to provide general and cost effective routes to such ligands.
In a first aspect, this invention provides a straightforward, efficient and cost effective process for the preparation of a 4,5-bisimino-[1,3]dithiolane or a 2,3-bisimino-[1,4]dithiane of general formula I, useful as ligands for olefin polymerization catalysts; 
wherein an oxalamide of general formula II 
is reacted with a reagent capable of transforming an amide to a thioamide, which is then reacted with a reagent of general formula III; 
wherein,
R and R1 are each, independently hydrocarbyl, substituted hydrocarbyl, heteroatom connected hydrocarbyl or heteroatom connected substituted hydrocarbyl;
Q is hydrocarbyl or substituted hydrocarbyl; and
X and Y1 are each, independently, a leaving group.
In a second aspect, this invention relates to a straightforward, efficient and cost effective process for the preparation of compounds of the general formula IV, useful as ligands for olefin polymerization catalysts, in a single reactor, without isolation of any intermediates; 
wherein a diketone of general formula V is reacted with a protected hydrazine in the presence of an acid to form a protected amino pyrrole, the resultant protected amino pyrrole is then reacted with an xcex1-diketone of general formula VI in the presence of an acid; 
wherein:
R5a and R5b are each, independently, hydrocarbyl, substituted hydrocarbyl, heteroatom connected hydrocarbyl or heteroatom connected substituted hydrocarbyl;
R6a is H, hydrocarbyl, substituted hydrocarbyl, heteroatom connected hydrocarbyl or heteroatom connected substituted hydrocarbyl; and
R7a and R7b are each hydrocarbyl, substituted hydrocarbyl, heteroatom connected hydrocarbyl, or heteroatom connected substituted hydrocarbyl.
In a first aspect, this invention relates to a process for the preparation of a 4,5-bisimino-[1,3]dithiolane or a 2,3-bisimino-[1,4]dithiane of general formula I by reacting a substituted oxalamide of general formula II with a reagent capable of transforming an amide to a thioamide to form a dithiooxalamide compound. The second step of the process involves reaction of the dithiooxalamide compound with a compound of general formula III to provide the 4,5-bisimino-[1,3]dithiolane or 2,3-bisimino-[1,4]dithiane of general formula I. This process, along with preferred embodiments, is described in more detail in the discussion and examples below.
The oxalamide may be any oxalamide of general formula II, which may be prepared by any number of methods known to those skilled in the art, including, but not limited to, reaction of oxalic dihydrazide with a 1,4-diketone and reaction of a primary amine with oxalyl chloride. Preferred R and R1 groups in general formula II are chosen from the group consisting of 
wherein:
R2a-2c are each, independently, H, hydrocarbyl, substituted hydrocarbyl, heteroatom connected hydrocarbyl or heteroatom connected substituted hydrocarbyl; R3a-3b are each, independently hydrocarbyl, substituted hydrocarbyl, heteroatom connected hydrocarbyl or heteroatom connected substituted hydrocarbyl; and R4a is H, hydrocarbyl, substituted hydrocarbyl, heteroatom connected hydrocarbyl or heteroatom connected substituted hydrocarbyl. Preferably R2a and R2c are each, independently, hydrocarbyl, substituted hydrocarbyl, heteroatom connected hydrocarbyl or heteroatom connected substituted hydrocarbyl. More preferably, R2a and R2c are each, independently, hydrocarbyl or substituted hydrocarbyl. Examples of suitable R2a and R2c groups include, but are not limited to, methyl, ethyl, isopropyl, isobutyl, tert-butyl, phenyl, 4-tert-butyl phenyl, 4-methyl phenyl, 4-methoxy phenyl, 4-trifluoromethyl phenyl, 4-nitro phenyl and 3,5-diphenyl phenyl.
Preferably, R3a and R3b are each, independently, hydrocarbyl or substituted hydrocarbyl. Examples of suitable R3a and R3b groups include, but are not limited to, methyl, ethyl, isopropyl, isobutyl, tert-butyl, phenyl, 4-tert-butyl phenyl, 4-methyl phenyl, 4-methoxy phenyl, 4-nitro phenyl and 3,5-diphenyl phenyl.
Preferably, R4a is H, hydrocarbyl or substituted hydrocarbyl. Examples of suitable R4a groups include, but are not limited to, H, methyl, ethyl, isopropyl, tert-butyl, isobutyl, phenyl, xe2x80x94COOR5, xe2x80x94COR, xe2x80x94CONR52, xe2x80x94CONHR5, cyano and nitro; wherein R5 is hydrocarbyl or substituted hydrocarbyl. Examples of suitable R5 groups include, but are not limited to, methyl, ethyl, isopropyl, tert-butyl, isobutyl and phenyl.
Examples of a reagent capable of transforming an amide to a thioamide include, but are not limited to, P4S10 and 2,4-bis(4-methoxyphenyl)-1,3-dithia-2,4-diphosphetane-2,4-disulfide.
The first step of the process may be run in an inert solvent, preferably toluene or xylene. When phosphorous pentasulfide is used as the source of sulfur, the reaction may be conducted at temperatures ranging from about 25 to about 200xc2x0 C., preferably at temperatures ranging from about 75 to about 150xc2x0 C. With other sources of sulfur, the preferred temperature range will generally be similar but will best be determined by routine experimentation. Pressures at or above about 1 atm are preferred.
Step two of the process to prepare a 4,5-bisimino-[1,3]dithiolane or a 2,3-bisimino-[1,4]dithiane of general formula I involves reaction of the dithiooxalamide formed in step (i) of the process with a compound of general formula III; wherein Q is hydrocarbyl or substituted hydrocarbyl; and X and Y1 are each, independently, leaving groups. Preferably, Q is xe2x80x94CH2CH2xe2x80x94, xe2x80x94CH2xe2x80x94, xe2x80x94COxe2x80x94 or xe2x80x94CSxe2x80x94; more preferably, Q is xe2x80x94CH2CH2xe2x80x94. When X and Y1 are both bromo and Q is xe2x80x94CH2CH2xe2x80x94, the reaction may be conducted at temperatures ranging from about 0 to about 100xc2x0 C., preferably at temperatures ranging from about 25 to about 50xc2x0 C. With other X, Y1, and Q, the preferred temperature range will generally be similar but will best be determined by routine experimentation. Pressures at or above about 1 atm are preferred.
A xe2x80x9cleaving groupxe2x80x9d is any species that can be expelled by a nucleophile in an SN2 reaction or is easily dissociated in an SN1 reaction. Examples of suitable leaving groups include, but are not limited to, chloride, bromide, p-toluene sulfonate, methane sulfonate and trifluoromethane sulfonate. Preferably, X and Y1 are each, independently, bromide.
Step (ii) of the process may further comprise a base to aid in the removal of the acidic dithiooxalamide proton. Preferably, the base is an alkali metal hydroxide or ammonium hydroxide. Preferred alkali metal hydroxides are sodium hydroxide and potassium hydroxide.
Step (ii) of the process may be run in neat compound III, as a solution in an inert organic solvent, in a biphasic mixture of compound III and water, or as a biphasic mixture of an inert organic solvent and water. When the reaction is run as a biphasic mixture, a phase transfer catalyst may also be present. A non-limiting example of a phase transfer catalyst is tetrabutyl ammonium bromide.
In a second aspect, this invention relates to a process for the preparation of a compound of general formula IV in three steps, which may be carried out in a single reaction vessel without isolation of the intermediate products.
The first step of the process of the second aspect involves the condensation of a protected hydrazine with a diketone of general formula V in the presence of an acid and an alcohol solvent to provide a protected 2,5-disubstituted, optionally 3-substituted, 1-amino pyrrole. Examples of suitable protected hydrazines include, but are not limited to, tert-butyl carbazate and hydrazine carboxylic acid 2-trimethylsilanyl-ethyl ester. Examples of suitable diketones of general formula V include, but are not limited to, dibenzoyl ethane and 2-benzoyl-4-oxo-4-phenyl-butyric acid ethyl ester. Examples of suitable acids include, but are not limited to, acetic acid and para-toluene sulfonic acid. Examples of suitable alcohol solvents include, but are not limited to, methanol, ethanol and isopropanol. The reaction may be conducted at temperatures ranging from about 25 to about 150xc2x0 C., preferably at temperatures ranging from about 50 to about 115xc2x0 C. Pressures at or above about 1 atm are preferred.
The second step of the process of the second aspect involves deprotection of the 1-amino pyrrole prepared in the first step in the presence of an acid in an alcohol solvent. Examples of suitable acids include hydrochloric acid, trifluoroacteic acid, phosphoric acid and sulfuric acid. Examples of suitable alcohol solvents include methanol, ethanol and isopropanol. The reaction may be conducted at temperatures ranging from about 0 to about 200xc2x0 C., preferably at temperatures ranging from about 25 to about 115xc2x0 C. Pressures at or above about 1 atm are preferred.
The third step of the process of the second aspect involves the condensation of the 1-amino pyrrole prepared in the second step, with an xcex1-diketone of general formula VI in the presence of an acid and alcohol solvent. Examples of suitable xcex1-diketones include, but are not limited to, 2,3-butanedione, benzil and 3,4-hexanedione. Examples of suitable acids include, but are not limited to, hydrochloric acid, sulfuric acid and phosphoric acid. Examples of suitable alcohol solvents include, but are not limited to, methanol, ethanol and isopropanol. The reaction may be conducted at temperatures ranging from about 0 to about 150xc2x0 C., preferably at temperatures ranging from about 25 to about 115xc2x0 C. Pressures at or above about 1 atm are preferred.
R5a and R5b are each, independently, hydrocarbyl or substituted hydrocarbyl, more preferably phenyl, 4-trifluoromethylphenyl, 4-tert-butylpehnyl or 4-methylphenyl.
R6a is H, hydrocarbyl, substituted hydrocarbyl, heteroatom connected hydrocarbyl or heteroatom connected substituted hydrocarbyl. Preferably, R6a is H, methyl, hydroxymethyl, cyano, nitro or xe2x80x94COOR8a, wherein R8a is hydrocarbyl or substituted hydrocarbyl, preferably methyl or ethyl.
R7a and R7b are each hydrocarbyl or substituted hydrocarbyl. Preferably, R7a and R7b are each, independently, methyl, ethyl, phenyl, aryl, or isopropyl. Additionally, R7a and R7b may be linked to form a bridging group. Preferred bridging groups include, but are not limited to 1,2-phenylene and 1,8-naphthylene.
A xe2x80x9chydrocarbylxe2x80x9d group means a monovalent or divalent, linear, branched or cyclic group which contains only carbon and hydrogen atoms. Examples of monovalent hydrocarbyls include the following: C1-C20 alkyl; C1-C20 alkyl substituted with one or more groups selected from C1-C20 alkyl, C3-C8 cycloalkyl, and aryl; C3-C8 cycloalkyl; C3-C8 cycloalkyl substituted with one or more groups selected from C1-C20 alkyl, C3-C8 cycloalkyl, and aryl; C6-C14 aryl; and C6-C14 aryl substituted with one or more groups selected from C1-C20 alkyl, C3-C8 cycloalkyl, and aryl; where the term xe2x80x9carylxe2x80x9d preferably denotes a phenyl, napthyl, or anthracenyl group. Examples of divalent (bridging) hydrocarbyls include: xe2x80x94CH2xe2x80x94, xe2x80x94CH2CH2xe2x80x94, xe2x80x94CH2CH2CH2xe2x80x94, naphthalene-1,8-diyl, and 1,2-phenylene.
A xe2x80x9csubstituted hydrocarbylxe2x80x9d refers to a monovalent or divalent hydrocarbyl substituted with one or more heteroatoms. Examples of monovalent substituted hydrocarbyls include: 2,6-dimethyl-4-methoxyphenyl, 2,6-diisopropyl-4-methoxyphenyl, 4-cyano-2,6-dimethylphenyl, 2,6-dimethyl-4-nitrophenyl, 2,6-difluorophenyl, 2,6-dibromophenyl, 2,6-dichlorophenyl, 4-methoxycarbonyl-2,6-dimethylphenyl, 2-tert-butyl-6-chlorophenyl, 2,6-dimethyl-4-phenylsulfonylphenyl, 2,6-dimethyl-4-trifluoromethylphenyl, 2,6-dimethyl-4-trimethylammoniumphenyl (associated with a weakly coordinated anion), 2,6-dimethyl-4-hydroxyphenyl, 9-hydroxyanthr-10-yl, 2-chloronapth-1-yl, 4-methoxyphenyl, 4-nitrophenyl, 9-nitroanthr-10-yl, xe2x80x94CH2OCH3, cyano, trifluoromethyl, and fluoroalkyl. Examples of divalent (bridging) substituted hydrocarbyls include: 4-methoxy- 1,2-phenylene, 1-methoxymethyl-1,2-ethanediyl, 1,2-bis(benzyloxymethyl)-1,2-ethanediyl, and 1-(4-methoxyphenyl)-1,2-ethanediyl.
A xe2x80x9cheteroatom connected hydrocarbylxe2x80x9d refers to a group of the type E1(hydrocarbyl), E2H(hydrocarbyl), or E2(hydrocarbyl)2, where E1 is an atom selected from Group 16 and E2 is an atom selected from Group 15.
A xe2x80x9cheteroatom connected substituted hydrocarbylxe2x80x9d refers to a group of the type E1(substituted hydrocarbyl), E2H(substituted hydrocarbyl), or E2(substituted hydrocarbyl)2, where E1 is an atom selected from Group 16 and E2 is an atom selected from Group 15.
A xe2x80x9cbridging groupxe2x80x9d refers to an atom or group which links two or more groups, which has an appropriate valency to satisfy its requirements as a bridging group. Suitable examples include divalent or trivalent hydrocarbyl, substituted hydrocarbyl, heteroatom connected hydrocarbyl, heteroatom connected substituted hydrocarbyl, substituted silicon(IV), boron(III), N(III), P(III), and P(V), xe2x80x94C(O)xe2x80x94, xe2x80x94SO2xe2x80x94, xe2x80x94C(S)xe2x80x94, xe2x80x94B(OMe)xe2x80x94, xe2x80x94C(O)C(O)xe2x80x94, O, S, and Se. In some cases, the groups which are said to be xe2x80x9clinked by a bridging groupxe2x80x9d are directly bonded to one another, in which case the term xe2x80x9cbridging groupxe2x80x9d is meant to refer to that bond.
A further understanding can be obtained by reference to certain specific examples which are provided herein for purpose of illustration only and are not intended to be limiting.